Project Summary End-stage heart failure (HF) is a debilitating condition that can only be cured by orthotopic heart transplantation (OHT). Because the availability of donor organs is limited, clinicians must carefully select patients for this lifesaving therapy who are likely to have a favorable outcome. Pulmonary hypertension (PH) is a common comorbidity seen in patients with HF that can preclude OHT, especially if pulmonary vascular resistance (PVR) is elevated above 3 Wood units (WU), as this condition is associated with poor survival after OHT. Left ventricular assist devices (LVADs) improve survival in end-stage HF and can result in normalization of PVR in some HF patients. However, the mechanisms by which LVADs result in PVR normalization are unknown. Furthermore, 40?60% of patients may never achieve PVR normalization with LVAD therapy, and it is difficult to identify these patients prior to LVAD implantation. Because LVAD implantation is a highly morbid procedure resulting in irreversible lifestyle changes for patients, a prediction tool to identify patients at high likelihood of achieving PVR normalization with LVAD therapy would help patients and clinicians make more informed decisions about proceeding with LVAD implantation in patients with elevated PVR. In the proposed research, we will use multivariable modeling to identify patient factors associated with changes in PVR after LVAD implantation to shed light on the mechanisms of pulmonary vascular remodeling with LVAD therapy. We will also develop a prediction model for PVR normalization among patients with elevated PVR > 3 WU at baseline. To accomplish these aims, we will use data from the International Society for Heart and Lung Transplantation Registry for Mechanically Assisted Circulatory Support (IMACS), the largest registry of contemporary LVAD recipients in the world. The IMACS registry includes over 14000 patients from 35 countries and is uniquely able to support the proposed analyses due to its large size. Based on this research, clinicians will gain insight into the mechanisms of pulmonary vascular remodeling in end-stage heart failure that can be used to spark new therapeutic strategies for patients with heart failure and PH. This research will also provide clinicians a tool that can be used for patients that are ineligible for OHT because of PH to help them make more informed decisions that are consistent with their values and goals of treatment.